Introduction

Ethanol-induced gastric ulcers are common and the treatment options are limited. Escin, a extract from the horse chestnut plant, has been proven to have therapeutic effects in improving inflammation, edema, and vascular permeability. However, its effects and mechanisms on ethanol-induced gastric mucosal injury are not yet clear.

Aims & Methods

This study aims to explore the protective effect of Escin on ethanol-induced gastric mucosal injury and its potential mechanisms, providing a new drug choice for the treatment of ethanol-induced gastric ulcers. For this purpose, a control, ethanol, ethanol+Escin , and ethanol+omeprazole groups were established in male SD rats to compare and analyze the ulcer index and histopathological scores of each group. The network pharmacology approach was used to predict potential targets of Escin related to gastric ulcers. Apoptotic proteins, NF-κb inflammatory pathway proteins, inflammatory factors, and related mRNA expression were analyzed by methods such as Immunofluorescence (IF), Immunohistochemistry (IHC), Western Blot (WB), real-time quantitative fluorescence PCR (q-PCR), and enzyme-linked immunosorbent assay (Elisa). Furthermore, an ethanol-induced GES-1 cell injury model was established to evaluate the protective effect of Escin. Finally, Transcriptomic sequencing was performed to identify key regulatory genes.

Results

The study found that Escin significantly reduced the damage of ethanol to gastric mucosal tissues. Network pharmacology analysis predicted that Escin is closely related to inflammatory pathways such as NF-κb in the treatment of gastric ulcers. IHC and WB results showed that Escin reduced the loss of gastric mucosal surface markers MUC5AC, TFF2, and gastric mucosal barrier protein O-ccludin, inhibited the expression of inflammatory factors IL-1β, IL-6, TNF-α, and apoptosis-related proteins BAX, Caspase-3, and promoted the expression of anti-apoptotic protein BCL-2. IF further revealed that Escin prevented the nuclear translocation of NF-κb, thereby inhibiting the activation of the NF-κb pathway. Elisa results showed a decrease in inflammatory factor levels in the plasma of rats in the Escin group, while q-PCR results demonstrated that Escin downregulated the expression levels of inflammatory factor mRNA in gastric tissues. Cell proliferation experiments also confirmed the protective effect of Escin against ethanol-induced damage. Finally, Transcriptomic analysis revealed significant upregulation of 27 inflammation-related genes in ethanol-treated gastric tissues. Notably, nine genes—Birc3, Bcl3, SOCS1, SOCS3, Ccl2, Cx3cl1, Pim1, SGK1, and OSMR—were identified as positive regulators of the TNF-α/NF-κB signaling axis through functional annotation and pathway enrichment analysis.

Conclusion

Escin exerts a protective effect on ethanol-induced gastric mucosal damage by inhibiting the TNF-α/NF-κB pathway, reducing the expression of inflammatory factors and the level of cell apoptosis. Escin, as a novel therapeutic drug for ethanol-induced gastric ulcers, has certain clinical translational application value, but further clinical trials are needed to confirm the results.

Introduction

Eight hospitals in the southwest of the Netherlands collaborate to improve inflammatory bowel disease (IBD) care. To achieve this, a care pathway (CP) was developed for treating IBD with biologics and small molecules. This CP addresses initiation and switching of therapy, as well as diagnostic testing and treatment follow-up (1).

Aims & Methods

This study aimed to estimate the causal effect of the CP on costs and quality of life, and to evaluate whether the CP is cost-effective.

A cost-effectiveness analysis was conducted from a societal perspective. The CP was implemented in six hospitals, with two control hospitals. Costs were assessed during a baseline period (December 2020–December 2021) and an intervention period (March 2022–March 2023). Quality-adjusted life years (QALYs) were derived from the EQ-5D-5L. A difference-in-differences (DiD) analysis was conducted and the incremental cost-effectiveness ratio (ICER) was calculated.

Results

A total of 1,173 patients were included (intervention n=841, control n=332). Baseline costs per patient were €23,259.96 in intervention hospitals, and €22,837.93 in control hospitals. During the intervention period costs decreased to €20,959.76 in intervention hospitals. This reduction was not observed in control hospitals (€22,191.21). The DiD-analysis showed cost savings of €-1,653.48. QALYs did not change. The ICER was located in the southeast quadrant of the cost-effectiveness plane, with a high probability of achieving a net monetary benefit exceeding €0 compared to standard care.

Conclusion

The implementation of a CP for the treatment of IBD with biologics and small molecules is cost-effective, it reduces healthcare costs while maintaining quality of life. Therefore, adoption of care pathways in care for complex diseases should be considered.

References

1. van Linschoten RCA, van Leeuwen N, Nieboer D, Birnie E, Scherpenzeel M, Verweij KE, et al. Value-based care pathway for inflammatory bowel disease: a protocol for the multicentre longitudinal non-randomised parallel cluster IBD Value study with baseline period. BMJ Open. 2022;12(1):e050539

Disclosure

Drs. Visser received a speaker fee from Lilly outside the submitted work.
Prof. Dr. van der Woude reports grants from Pfizer and Janssen and personal fees from AbbVie and Celltrion outside the submitted work.
Dr. van Noord reports personal fees from Janssen, Takeda, and Falk outside the submitted work.
Dr. West reports personal fees from AbbVie, Janssen, and Pfizer outside the submitted work.

Introduction

Endoscopic placement of self-expandable metallic stents (SEMS) for malignant colorectal obstruction near the dentate line is technically challenging because of the difficulty faced in the precise alignment of the distal edge of the stent with the distal end of the lesion. Furthermore, after stenting, lesions close to the dentate line often induce anal pain. Therefore, positioning of the distal end of the stent at an adequate distance from the dentate line is crucial for reducing discomfort. A proximally release-type SEMS might be particularly advantageous in such cases.

Aims & Methods

This study aimed to assess the safety and efficacy of proximally release-type SEMS for malignant colorectal obstruction placed within 10 cm from the dentate line. The study retrospectively analyzed 12 consecutive patients who had undergone SEMS placement between May 2019 and March 2024 at our institution. The clinical outcomes, technical and clinical success rates, adverse events, and prognosis were evaluated.

Results

The median age of the subjects was 70.5 years, and included five (41.7%) men and seven (58.3%) women. The causes of obstruction were primary colorectal cancer (six patients), gastric cancer (five patients), and cervical cancer (one patient). Colorectal Obstruction Scoring System (CROSS) scores prior to SEMS placement were 0 (2 patients), 1 (10 patients). Tumor locations included Rs in two patients, Ra in two, and Rb in eight patients, with the median distance from the dentate line being 4.5 cm (range: 2–10 cm). The indications for SEMS placement were bridge to surgery (BTS) in four cases and palliation (PAL) in eight cases. The technical success rate was 91.7% (11/12), and the clinical success within seven days was also 91.7% (11/12). Early adverse events (within seven days) included one case of stent migration (8.3%) No cases of perforation, bleeding, or reobstruction were observed. All BTS patients underwent successful laparoscopic surgeries and no recurrence has been observed to date. Among the PAL cases, one patient experienced stent migration 314 days after SEMS placement. The migrated stent was manually extricated under general anesthesia.

Conclusion

The proximally release-type colonic stent was effective for treating malignant colorectal obstruction near the dentate line since it facilitated placement of the stent in the right position. It might be the primary option for malignant colorectal obstruction near the dentate line, and can contribute to the expansion of indications for colorectal stent placement for lesions near the anal verge.

Introduction

Fecal immunochemical test (FIT), widely used in colorectal cancer screening, has emerged as a potential biomarker of endoscopic activity in inflammatory bowel disease (IBD). Compared to fecal calprotectin, FIT offers greater standardization, automation and availability, with simpler handling and potentially better adherence. Its implementation could streamline non-invasive monitoring, but its diagnostic accuracy in IBD remains unclear. We therefore conducted a systematic review and meta-analysis to evaluate its performance.

Aims & Methods

Selection of studies: assessing the accuracy of FIT to estimate endoscopic activity in IBD patients. Search strategy: electronic bibliographical searches. Data synthesis: meta-analyses of the FIT were performed combining the sensitivity (Se), specificity (Sp), likelihood ratios (LRs), and area under de curve (AUC) values of summary receiver operating characteristic (ROC) curves of the individual studies. Heterogeneity among the studies was assessed by the I-squared (I²) statistic.

Results

Eighteen studies (table 1) met the inclusion criteria: 12 focused on ulcerative colitis (UC), 4 on both UC and Crohn’s disease (CD), and 2 on CD alone. Twelve studies employed the standard cut-off for FIT provided by the manufacturer or used the same cut-off as for colorectal cancer screening (usually considered the common threshold), while 6 studies estimated their optimal cut-off values. When we considered all studies (including 1,812 patients and 2,137 assessments), the accuracy of FIT for the diagnosis of endoscopic activity was (pooled values): Se: 0.66, Sp: 0.83, LR+: 4.96, and LR-: 0.38, respectively, with an AUC of 0.86. Significant heterogeneity was found among the Se (I² 89%) and Sp (I² 86%) of different studies. Most of the available studies were based exclusively on patients with UC (including 1,554 patients and 1,904 assessments), so we performed a subgroup analysis including only this type of IBD, finding a pooled Se, Sp, LR+ and LR- of 0.69, 0.82, 5.35 and 0.31 respectively, with an AUC of 0.88. On the other hand, in patients with CD (327 patients, 302 assessments), the corresponding values were 0.55, 0.85, 3.2 and 0.58, with an AUC of 0.73. ROC curve analysis showed that FIT had a higher diagnostic performance in UC patients.

Conclusion

FIT demonstrates moderate-to-high diagnostic accuracy for detecting endoscopic activity in IBD, particularly in UC. Therefore, FIT may represent a promising non-invasive tool for assessing IBD disease activity. However, significant heterogeneity among studies underscores the need for further research to optimize cut-off values and define the role of FIT in routine IBD monitoring.

Introduction

The ulcers after duodenal endoscopic resection (ER) are exposed to bile and pancreatic juice, therefore delayed perforation and bleeding are major complications. The condition caused by perforation can become serious, requiring surgical treatment and even death.
As a preventive measure, the suture of the ulcer after ER has been reported to be effective. There are two main suture methods: endo clips and laparoscopic suturing.

Aims & Methods

The aim of this retrospective study is to investigate the outcome of Endoscopic submucosal dissection (ESD) and laparoscopic and endoscopic co-operative surgery (D-LECS) for superficial non-ampullary duodenal epithelial tumors (SNADETs). ESD ulcer was sutured with endo clips in ESD group, and with laparoscopic suture in D-LECS group.
One hundred seventy-eight patients with SNADETs who underwent ESD and 41 patients with SNADETs who underwent D-LECS from November 2002 to February 2025 were investigated outcome of procedure. The patient’s characteristics in ESD and D-LECS were as follows. male/female: 124/54 and 27/14, median age: 62 (37-86) and 67 (37-83) years old, location of the tumor (bulbs/2^nd/3rd portion): 15/139/24 and 0/32/9, major macroscopic type (0-I/0-IIa/0-IIb/0-IIc): 5/91/1/81 and 1/32/0/8. Only major macroscopic type was difference significantly between ESD and D-LECS (p=0.001). SM1 was defined as submucosal invasion of less than 500 μm, and SM2 was defined as deeper. R0 was defined as lateral and vertical margin negative, and lymph-vascular involvement negative. DLECS was selected when it was predicted that endo clips suture might be insufficient, or when the scope maneuverability was poor.

Results

1. Median procedure time was 36 (7-245) in ESD and 351 (202-673) minutes in D-LECS, respectively(p<0.001). Median diameter of resected specimen was 17 (8-66) and 38 (17-70) mm(p<0.001). Median diameter of resected specimen and tumor was 10 (2-63) and 27 (14-52) mm(p<0.001). Intramucosal tumor (Vienna classification category 3 to 5.1) /T1bSM (category 5.2): 176/2 and 37/4 (p=0.01).
2. The en bloc resection was 90% (161/178) and 95% (39/41), respectively (p=0.53). R0 resection rate was 85% (151/178) and 88% (36/41) (p=0.62).
3. The rate of complete suture for ESD ulcer was 92% (164/178) in ESD group and 100% in D-LECS group, respectively (p=0.07). The details in D-LECS are as follows: 27% (11/41) of laparoscopic suture alone and 73% (30/41) of laparoscopic and endo clips suture.　
4. Complications: intraoperative perforation was 2% (4/178) and 10% (4/41) (p=0.04). Intraoperative bleeding requiring blood transfusion was 0% and 0%. Delayed perforation was 1% (2/178) and 0% (p=1.00). Delayed bleeding was 2% (4/178) and 0% (p=1.00).
Discussion:
1. The DLECS group treated larger cases and had more intraoperative perforations, but no delayed perforation or bleeding was observed.
2. Laparoscopic suture of the pancreatic side was not possible, but complete suture was achieved in all cases by adding a clip from the luminal side endoscopically.
3. Even after complete suture by ESD, delayed perforation can still occur. Therefore, if abdominal pain occurs, a CT scan should be performed immediately.　And if perforation is suspected, laparoscopic re-suture should be considered immediately.

Conclusion

DLECS for large SNADETs has similar outcome of ESD, and is an effective treatment. DLECS should be considered when complete suture with a clip is predicted to be difficult or when the scope maneuverability was poor.

References

None

Introduction

The term "cold" describes a range of respiratory illnesses primarily triggered by viral infections. Colds are the most common infectious diseases in the world, affecting daily life and increasing healthcare costs and lost productivity. Cold symptoms typically emerge 2-3 days after viral exposure. Children and those with a compromised immune system may experience more severe complications. The gut microbiota is directly involved in immune function, and probiotics can restore gut balance and enhance immunity. Specific probiotic strains, including L. plantarum PBS077, L. acidophilus PBS066, and B. lactis BL050, have demonstrated antimicrobial and anti-inflammatory properties.

Aims & Methods

This study aims to evaluate the effects of a dietary supplement containing L. plantarum PBS077, L. acidophilus PBS066, and B. lactis BL050 probiotics on relieving cold symptoms in healthy individuals, focusing on its potential to enhance immune response and improve quality of life (QoL). This randomized, double-blind, placebo-controlled clinical trial was conducted in Italy in winter from 2022 to 2024, involving 65 healthy volunteers aged 18-44. Participants were assigned to two groups: 40 received a probiotic treatment with specific strains (L. plantarum PBS077, L. acidophilus PBS066, B. lactis BL050), B6 and B12 vitamins, folic acid, and bulking agents (Probiotic), while 25 received a placebo, consisting of bulking agents, B6 and B12 vitamins and folic acid, without probiotics (Placebo). Participants took one capsule daily for 12 weeks, with assessments conducted at baseline (T0), after treatment (T1), and 6 weeks post-treatment (T2). Cold symptoms and quality of life (QoL) were assessed using a validated questionnaire (WURSS-21), and systemic inflammation was evaluated through serum cytokine levels (IFN-γ and IL-10) at each time point. The total observation period lasted 18 weeks.

Results

Probiotics were associated with a shorter average duration of cold symptoms (4.5 vs. 6.7 days for the Placebo), with a 32.7% reduction in symptom duration, p<0.05. At T1, fever occurred in 8 out of 40 participants in the Probiotic group (20%) and in 7 out of 25 participants in the Placebo group (28%), p<0.05. Additionally, at T1, muscle pain was reported by 20% of the Probiotic group (8 out of 40) vs. 44% of the Placebo group (11 out of 25). By T2, muscle pain occurred in 17.5% of the Probiotic group (7 out of 40) and 20% of the Placebo group (5 out of 25), p<0.05. At T1, the pro-inflammatory cytokine IFN-γ levels decreased in the Probiotic group compared to T0 (17,946±2,857 vs. 28,962±4,143 pg/ml, p < 0.05) and increased in the Placebo group compared to T0 (22,279±3,538 vs. 19,432±3,143 pg/ml, p < 0.05). Though not statistically significant, at T1 the Probiotic group had higher levels of IL-10 compared to T0 (266,98±78,432 vs. 240,967± 70,238, p>0.05).

Conclusion

The probiotic mix alleviated symptoms in patients with colds and reduced levels of the pro-inflammatory cytokine IFN-γ, demonstrating anti-inflammatory properties.

References

1.Eccles, R. Understanding the Symptoms of the Common Cold and Influenza. Lancet Infect. Dis. 2005, 5, 718–725, doi:10.1016/S1473-3099(05)70270-X.
2.Wiertsema, S.P.; van Bergenhenegouwen, J.; Garssen, J.; Knippels, L.M.J. The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients 2021, 13, doi:10.3390/nu13030886.
3.Carabotti, M.; Scirocco, A.; Maselli, M.A.; Severi, C. The Gut-Brain Axis: Interactions between Enteric Microbiota, Central and Enteric Nervous Systems. Ann. Gastroenterol. 2015, 28, 203–209.
4. Ghosh, S.; Whitley, C.S.; Haribabu, B.; Jala, V.R. Regulation of Intestinal Barrier Function by Microbial Metabolites. Cell. Mol. Gastroenterol. Hepatol. 2021, 11, 1463–1482, doi:10.1016/j.jcmgh.2021.02.007.
5. De Giani, A.; Bovio, F.; Forcella, M.; Fusi, P.; Sello, G.; Di Gennaro, P. Identification of a Bacteriocin-like Compound from Lactobacillus Plantarum with Antimicrobial Activity and Effects on Normal and Cancerogenic Human Intestinal Cells. AMB Express 2019, 9, 88, doi:10.1186/s13568-019-0813-6.